It is well established that certain pulmonary toxins and carcinogens act on specific cell types of the rodent lungs. Metabolism studies in vivo, or experiments using whole organ homogenates and fractions, may therefore not be suited to detect metabolic pathways operative in such specific cell types. It is the objective of this project to isolate and selectively grow the major epithelial cell types of the rat and hamster lung and to use them for comparative studies on their biology and response to toxins, carcinogens and anticancer drugs. Type II cells and mucous cells of the rat lung have been successfully isolated as have been hamster type II cells. Efforts are currently being made to isolate hamster neuroendocrine cells. The morphology of the isolated type II and mucous cells has been characterized in detail by scanning and transmission electron microscopy. Comparative experiments are underway on the effect of the pulmonary agents diethylnitrosamine, 4-ipomeanol and BCNU on these cell types.